crossing96/oncoscreening huggingface dataset:
lncRNA UCA1 promotes tumor progression by targeting SMARCD3 in cervical cancer.	Long noncoding RNA urothelial carcinoma associated 1 (UCA1) has been identified as a key molecule in human cancers. However, its functional implications remain unspecified in the context of cervical cancer (CC). This research aims to identify the regulatory mechanism of UCA1 in CC. UCA1 was identified through microarray and confirmed through a quantitative real-time polymerase chain reaction. Proteins that bind with UCA1 were recognized using RNA pull-down assays along with RNA immunoprecipitation. Ubiquitination assays and coimmunoprecipitation were performed to explore the molecular mechanisms of the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily d, member 3 (SMARCD3) downregulated in CC. The effects of UCA1 and SMARCD3 on the progression of CC were investigated through gain- and loss-of-function assays and xenograft tumor formation in vivo. In this study, UCA1 was found to be upregulated in CC cells as well as in human plasma exosomes for the first time. Functional studies indicated that UCA1 promotes CC progression. Mechanically, UCA1 downregulated the SMARCD3 protein stabilization by promoting SMARCD3 ubiquitination. Taken together, we revealed that the UCA1/SMARCD3 axis promoted CC progression, which could provide a new therapeutic target for CC.	bladder
Bioinformatics analysis of CMTM family in pan-cancer and preliminary exploration of CMTM6 in bladder cancer.	BACKGROUND: The chemokine-like factor (CKLF)-like Marvel transmembrane structural domain (CMTM) family is widely expressed in the tumor and immune systems and is essential in human cancer progression. However, the multi-omic profile of CMTM family genes and their role in tumor patient prognosis and immune microenvironment have not been explored. METHODS: We collected data from 33 cancers and 33 non-cancers and then comprehensively analyzed the basal expression levels of CMTM family genes in normal human tissues as well as abnormal expression in diseases, genomic alterations, diagnostic and prognostic roles, subcellular localization, pathway enrichment, the immune microenvironment, associations with immune checkpoints, and drug sensitivities as well as to predict the immunotherapeutic response of patients to ICIs and targeting of small molecule drugs, the above results were validated by immunohistochemical staining, pathology sections and experiments. We also performed protein docking of immune checkpoints binding to CMTM6 and screening of small molecule drugs targeting CMTM6 based on mass spectrometry results and molecular docking techniques. Finally, we experimentally confirmed the role of CMTM6 in bladder cancer. RESULTS: We found differential expression and diagnostic biomarker value of the CMTMs family in diseases (cancer and non-cancer). CMTMs were also found to play a key role in pan-cancer with the tumor microenvironment. CMTMs were closely associated with common immune checkpoints, TMB and MSI, so we scored CMTMs based on CMTMs expression in patients undergoing ICI, and patients with lower scores had better survival and showed higher immunotherapy response after immunotherapy. Finally, molecular docking was used to identify small molecule inhibitors that could target CMTM6 and binding poses of CMTM6 to other immune checkpoint genes. Finally, it was determined experimentally that knockdown of CMTM6 gene expression inhibited the proliferation and invasion of bladder cancer cells. CONCLUSIONS: Our findings provide a valuable strategy to guide the diagnostic and therapeutic direction of CMTM family genes in disease.	bladder
Summary of the Clinical Practice Guidelines for Upper Tract Urothelial Carcinoma 2023 by the Japanese Urological Association.	This article is an English translation of the Clinical Practice Guidelines for Upper Tract Urothelial Carcinoma (2nd edition) published in June 2023. The Japanese Urological Association's (JUA) Guidelines Committee on Upper Tract Urothelial Carcinoma (UTUC) created a 2023 update guideline to support clinicians' current evidence-based management of UTUC and to incorporate its recommendations into clinical practice. The new guideline adhered as closely as possible to the Minds Manual for Guideline Development 2020 ver. 3.0. Findings related to epidemiological, pathological, diagnosis, treatment, and follow-up were reviewed. In addition, seven clinical questions (CQs) were set to determine the grade of recommendation and level of evidence. Preconceptions and biases were removed from the preparation process, the overall evidence was evaluated appropriately, and recommendations were made after fully considering the balance between benefits and harms. Although the evidence is still insufficient to be taken up as a CQ, the latest important information is described in seven columns, and clinical issues that should be resolved in the future related to the CQ are described as recommendations for tomorrow. We hope that these guidelines will help medical professionals, patients, and their families involved in the treatment of UTUC in their decision-making, and hope that a critical review of these guidelines will lead to further refinements in the next edition.	bladder
Latest evidence on clinical outcomes and prognostic factors of advanced urothelial carcinoma in the era of immune checkpoint inhibitors: a narrative review.	The management of advanced (locally advanced or metastatic) urothelial carcinoma has been revolutionized since pembrolizumab was introduced in 2017. Several prognostic factors for advanced urothelial carcinoma treated with pembrolizumab have been reported, including conventional parameters such as performance status and visceral (especially liver) metastasis, laboratory markers such as the neutrophil-to-lymphocyte ratio, sarcopenia, histological/genomic markers such as programmed cell death ligand 1 immunohistochemistry and tumor mutational burden, variant histology, immune-related adverse events, concomitant medications in relation to the gut microbiome, primary tumor site (bladder cancer versus upper tract urothelial carcinoma) and history/combination of radiotherapy. The survival time of advanced urothelial carcinoma has been significantly prolonged (or 'doubled' from 1 to 2 years) after the advent of pembrolizumab, which will be further improved with novel agents such as avelumab and enfortumab vedotin. This review summarizes the latest evidence on clinical outcomes and prognostic factors of advanced urothelial carcinoma in the contemporary era of immune checkpoint inhibitors.	bladder
A case series of urinary bladder rhabdomyosarcoma in seven dogs.	BACKGROUND: Juvenile urinary bladder rhabdomyosarcoma (ubRMS) is a known entity; however, literature regarding its clinical behavior and endoscopic features is scarce. The aim of this study was to describe clinical and endoscopic features, and outcomes of ubRMS in dogs. CASE DESCRIPTION: Dogs undergoing transurethral endoscopy and with a histological diagnosis of ubRMS were retrospectively collected. Seven dogs with a median age of 18 months (range 6-32 months) were included in this retrospective, multicenter, and descriptive study. Median tumor size was 58 mm (range 30-65 mm), and tumor location was bladder neck in three cases, trigone in two cases, and bladder body in two cases. Two dogs had monolateral ureteral obstruction. Two dogs presented with regional lymphadenopathy and one dog had lung lesions suggestive of metastatic disease. A grape-like mass was reported in four cases and solid in two, with variable consistency (two friables, two firms, and two not reported). Tumor treatments included surgery in three cases, surgery, and adjuvant doxorubicin in one case, and palliative therapy in three cases. The overall median survival time (ST) was 45 days. STs were shorter (range 20-45 days) for dogs treated with palliative care than for dogs treated with curative-intent treatment (range 70-120 days). CONCLUSION: ubRMS should be considered as a differential diagnosis in young dogs presenting with bladder masses. In this study, ubRMS confirmed its aggressive clinical behavior. Surgery and chemotherapy seem to increase STs but the prognosis remains poor.	bladder
Long-term outcomes and cost savings of office fulguration of papillary Ta low-grade bladder cancer.	OBJECTIVES: To assess whether office-based fulguration (OF) under local anaesthesia for small, recurrent, pathological Ta low-grade (LG) non-muscle-invasive bladder cancer (NMIBC) is an effective alternative to transurethral resection of bladder tumour (TURBT), avoiding the costs and risks of procedure, and anesthesia. PATIENTS AND METHODS: Of 521 patients with primary TaLG NMIBC, this retrospective study included 270 patients who underwent OF during follow-up for recurrent, small, papillary LG-appearing tumours at a university centre (University Health Network, University of Toronto, Canada). We assessed the cumulative incidence of cancer-specific mortality (CSM) and disease progression (to MIBC or metastases), as well as possible direct cost savings. RESULTS: In the 270 patients with recurrent TaLG NMIBC treated with OF, the mean (sd) age was 64.9 (13.3) years, 70.8% were men, and 60.3% had single tumours. The mean (sd, range) number of OF procedures per patient was 3.1 (3.2, 1-22). The median (interquartile range) follow-up was 10.1 (5.8-16.2) years. Patients also underwent a mean (sd) of 3.6 (3.0) TURBTs during follow-up in case of numerous or bulkier recurrence. In all, 44.4% of patients never received intravesical therapy. The 10-year incidence of CSM and progression were 0% and 3.1% (95% confidence interval 0.8-5.4%), respectively. Direct cost savings in Ontario were estimated at $6994.14 (Canadian dollars) per patient over the study follow-up. CONCLUSIONS: This study supports that properly selected patients with recurrent, apparent TaLG NMIBC can be safely managed with OF under local anaesthesia with occasional TURBT for larger or numerous recurrent tumours, without compromising long-term oncological outcomes. This approach could generate substantial cost-saving to healthcare systems, is patient-friendly, and could be adopted more widely.	bladder
Prognostic Impact of the Modified 5-Item Frailty Index After Radical Nephroureterectomy in Patients With Upper Tract Urothelial Carcinoma: A Multicenter Retrospective Study.	INTRODUCTION: The modified 5-item frailty index can be used to evaluate frailty using 5 routinely encountered clinical variables. This study aimed to assess the impact of the modified 5-item frailty index in patients who underwent radical nephroureterectomy for upper tract urothelial carcinoma. PATIENTS AND METHODS: In this multicenter retrospective study, we calculated the modified 5-item frailty index scores of patients who underwent radical nephroureterectomy for upper tract urothelial carcinoma between 2010 and 2022. Patients were categorized into the high (≥2) and low (≤1) modified 5-item frailty index score groups. To assess the prognostic influence of the preoperative modified 5-item frailty index, we conducted Cox proportional regression analyses concerning progression-free, overall, and cancer-specific survival. RESULTS: Of 434 patients, 82, and 352 were classified into the high and low modified 5-item frailty index score groups, respectively. The high modified 5-item frailty index score group had significantly higher rates of severe surgical complications (P = .038) and ≥30 days of hospitalization (P = .049) and significantly worse progression-free (P = .012) and overall survival (P = .002) than the low modified 5-item frailty index score group. The multivariable Cox proportional hazard analysis revealed that a high modified 5-item frailty index score was independently associated with poor progression-free (P = .044), overall (P = .017), and cancer-specific survival (P = .005). CONCLUSION: The modified 5-item frailty index emerged as a significant predictive indicator of severe surgical complications and postoperative survival outcomes in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy.	bladder
Exploratory analyses of treatment subgroup interaction by PD-L1 status and according to PD-L1 expression in the JAVELIN Bladder 100 trial.	PURPOSE: Post hoc analysis of the JAVELIN Bladder 100 trial of avelumab maintenance in locally advanced/metastatic urothelial carcinoma (la/mUC) to determine the interaction by programmed death ligand 1 (PD-L1) status for overall survival (OS), and additional analyses of survival per a different PD-L1 expression cutoff of ≥ 1% in tumor cells or immune cells (TC/IC). METHODS: JAVELIN Bladder 100 data were used for the analysis of the interaction by PD-L1 status (per cutoff used in the trial) for OS and, additionally, OS and progression-free survival (PFS) analyses per a different ≥ 1% TC/IC PD-L1 expression cutoff (Ventana SP263 assay). RESULTS: No significant interaction between treatment and PD-L1 status was observed for OS. Clinically meaningful and robust survival data were observed in favor of avelumab using the different ≥ 1% TC/IC PD-L1 expression cutoff. CONCLUSIONS: These results demonstrate the benefit of avelumab maintenance in la/mUC regardless of PD-L1 expression, consistent with approved labels.	bladder
Phase II trial of afatinib in patients with advanced urothelial carcinoma with genetic alterations in ERBB1-3 (LUX-Bladder 1).	BACKGROUND: Preclinical and early clinical data suggest that the irreversible ErbB family blocker afatinib may be effective in urothelial cancers harbouring ERBB mutations. METHODS: This open-label, phase II, single-arm trial (LUX-Bladder 1, NCT02780687) assessed the efficacy and safety of second-line afatinib 40 mg/d in patients with metastatic urothelial carcinoma with ERBB1-3 alterations. The primary endpoint was 6-month progression-free survival rate (PFS6) (cohort A); other endpoints included ORR, PFS, OS, DCR and safety (cohorts A and B). Cohort A was planned to have two stages: stage 2 enrolment was based on observed antitumour activity. RESULTS: Thirty-four patients were enroled into cohort A and eight into cohort B. In cohorts A/B, PFS6 was 11.8%/12.5%, ORR was 5.9%/12.5%, DCR was 50.0%/25.0%, median PFS was 9.8/7.8 weeks and median OS was 30.1/29.6 weeks. Three patients (two ERBB2-amplified [cohort A]; one EGFR-amplified [cohort B]) achieved partial responses. Stage 2 for cohort A did not proceed. All patients experienced adverse events (AEs), most commonly (any/grade 3) diarrhoea (76.2%/9.5%). Two patients (4.8%) discontinued due to AEs and one fatal AE was observed (acute coronary syndrome; not considered treatment-related). CONCLUSIONS: An exploratory biomarker analysis suggested that basal-squamous tumours and ERBB2 amplification were associated with superior response to afatinib. CLINICAL TRIAL REGISTRATION: NCT02780687.	bladder
The addition of tislelizumab to gemcitabine and cisplatin chemotherapy increases thrombocytopenia in patients with urothelial carcinoma: A single-center study based on propensity score matching.	PURPOSE: Whether the addition of tislelizumab to gemcitabine and cisplatin (GC) chemotherapy increases the incidence of myelosuppression has not been well established. This study identified the risk factors for the development of myelosuppression in patients with urothelial carcinoma (UC) after receiving GC chemotherapy with or without tislelizumab. MATERIALS AND METHODS: We enrolled 192 UC patients who received GC with or without tislelizumab at the Affiliated Hospital of Xuzhou Medical University between July 2014 and November 2022. Patient baseline characteristics were included in the statistical analyses after adjusting for previously reported risk factors affecting survival using propensity score matching (1:1). Binary logistic regression analysis was used to identify the risk factors associated with posttreatment myelosuppression. RESULTS: A total of 192 patients were enrolled, of whom 96 were treated with tislelizumab plus gemcitabine and cisplatin (T + GC) and 96 with GC alone. The incidence of leukopenia, anemia, and thrombocytopenia of any grade was 50.0%, 70.8%, and 42.7%, respectively, in the T + GC group and 41.7%, 72.9%, and 20.8%, respectively, in the GC group. In multivariate analysis, patients aged over 70 years (OR = 2.486, 95% CI: 1.067-5.792, p = 0.035) and those who received T + GC (OR = 3.119, 95% CI: 1.576-6.173, p = 0.001) were more likely to develop thrombocytopenia. Patients aged over 70 years (OR = 3.213, 95% CI: 1.254-8.237, p = 0.015) were more likely to develop anemia, and patients with renal insufficiency (OR = 2.105, 95% CI: 1.035-4.280, p = 0.040) were more likely to develop leukopenia. Eventually, 99 (51.6%) patients with UC successfully completed all the treatment cycles. CONCLUSIONS: This study demonstrates that the addition of tislelizumab to GC chemotherapy led to a considerable increase in the occurrence of thrombocytopenia, whereas no significant changes were observed regarding anemia or leukopenia. It is crucial to fully inform patients at increased risk for myelosuppression of potential risks and closely monitor changes in their blood routines.	bladder
Interruptions in bladder cancer care during the COVID-19 public health emergency.	BACKGROUND: Academic and community urology centers participating in a pragmatic clinical trial in non-muscle-invasive bladder cancer completed monthly surveys assessing restrictions in aspects of bladder cancer care due to the COVID-19 Public Health Emergency. Our objective was to describe pandemic-related restrictions on bladder cancer care. METHODS: We invited 32 sites participating in a multicenter pragmatic bladder cancer trial to complete monthly surveys distributed through REDCap beginning in May 2020. These surveys queried sites on whether they were experiencing restrictions in the use of elective surgery, transurethral resection of bladder tumors (TURBT), radical cystectomy, office cystoscopy, and intravesical bacillus Calmette-Guerin (BCG) availability. Responses were collated with descriptive statistics. RESULTS: Of 32 eligible sites, 21 sites had at least a 50% monthly response rate over the study period and were included in the analysis. Elective surgery was paused at 76% of sites in May 2020, 48% of sites in January 2021, and 52% of sites in January 2022. Over those same periods, coinciding with COVID-19 incidence waves, TURBT was restricted at 10%, 14%, and 14% of sites, respectively, radical cystectomy was restricted at 10%, 14%, and 19% of sites, respectively, and cystoscopy was restricted at 33%, 0%, and 10% of sites, respectively. CONCLUSIONS: Bladder cancer care was minimally restricted compared with more pronounced restrictions seen in general elective surgeries during the COVID-19 pandemic.	bladder
The expression of SP263 in muscle invasive bladder carcinoma and its relationship with clinicopathological features.	CONTEXT: The expression of programmed cell death ligand1 (PDL1) is a research hotspot of immunotherapy. The treatment targeted for its expression has shown effectiveness in many tumors. OBJECTIVE: The aim of the study was to determine PD-L1 expression in urothelial carcinoma (UC) and to compare the PD-L1 expression in muscle invasive bladder carcinoma (MIBC) and upper urinary tract urothelial carcinoma (UTUC). The predictive value of CD8+ tumor-infiltrating lymphocyte (TIL) density for the diagnosis of PD-L1 positivity and the association between CD8+ TIL density and prognosis in MIBC were also explored. MATERIALS AND METHODS: Immunohistochemistry (IHC) staining for PD-L1 (SP263), CK5/6, CK20, CD44, and p53 was carried out using a 3D Histech digital scanner to scan and determine CD8+ TIL density. RESULTS: 122 patients received radical cystectomy, and the overall PD-L1 positivity was 34.43% (42/122). PD-L1 positivity in whole sections was higher than in tissue micro-array (TMA) (all P < 0.05). If multiple lesions were detected simultaneously, the number of patients with positive results increased from 42 to 49. The areas under the curve (AUCs) of CD8+ TIL density for the diagnosis of PD-L1 positivity were 0.739, 0.713, and 0.826. Univariate cox regression analysis demonstrated that high CD8+ TIL density and CD8(high)PDL1(+) were protective factors of overall survival (OS), and multivariate cox analyses showed that only CD8+ TIL density was an independent prognostic factor for OS. For UTUC, the overall PD-L1 expression was 40.0% (16/40). CONCLUSIONS: Our study results emphasize the importance of detecting PD-L1 expression in multiple tumor lesions from the same patient. In MIBC, CD8+ TIL density could be used as a prognostic marker for predicting the status of PD-L1 expression.	bladder
G3BP1 and SLU7 Jointly Promote Immune Evasion by Downregulating MHC-I via PI3K/Akt Activation in Bladder Cancer.	Immune checkpoint inhibitors (ICIs) show promise as second-line treatment for advanced bladder cancer (BLCA); however, their responsiveness is limited by the immune evasion mechanisms in tumor cells. This study conduct a Cox regression analysis to screen mRNA-binding proteins and reveals an association between Ras GTPase-activating protein-binding protein 1 (G3BP1) and diminished effectiveness of ICI therapy in patients with advanced BLCA. Subsequent investigation demonstrates that G3BP1 enhances immune evasion in BLCA cells by downregulating major histocompatibility complex class I (MHC-I) through phosphoinositide 3-kinase (PI3K)/Akt signaling activation. Mechanistically, G3BP1 interacts with splicing factor synergistic lethal with U5 snRNA 7 (SLU7) to form a complex with poly(A)-binding protein cytoplasmic 1 and eukaryotic translation initiation factor 4 gamma 1. This complex stabilizes the closed-loop structure of the mRNAs of class IA PI3Ks and consequently facilitates their translation and stabilization, thereby activating PI3K/Akt signaling to downregulate MHC-I. Consistently, targeting G3BP1 with epigallocatechin gallate (EGCG) impedes immune evasion and sensitizes BLCA cells to anti-programmed cell death (PD)-1 antibodies in mice. Thus, G3BP1 and SLU7 collaboratively contribute to immune evasion in BLCA, indicating that EGCG is a precision therapeutic agent to enhance the effectiveness of anti-PD-1 therapy.	bladder
Tumor-derived exosomal miR-1247-3p promotes angiogenesis in bladder cancer by targeting FOXO1.	Tumor-derived exosomes are highly correlated with tumor progression and angiogenesis. This study was designed to probe the role of tumor-derived exosomal miR-1247-3p in mediating the angiogenesis in bladder cancer. Exosomes isolation from the culture medium of normal or bladder cancer cell lines was performed using a differential centrifugation method. miR-1247-3p expression in exosomes and cells was detected by quantitative real-time PCR (qRT-PCR). The effect of exosomes on the angiogenesis of human umbilical vein endothelial cells (HUVECs) was assessed using cell counting kit-8 (CCK-8), transwell and tube formation assays. The interaction between miR-1247-3p and forkhead box protein O1 (FOXO1) was studied using luciferase reporter and RNA pull down assays. Exosomes were successfully isolated from T24, UM-UC-3, and SV-HUC-1 cells, as confirmed by corresponding identifications. Functional experiments revealed that exosomes derived from T24 and UM-UC-3 cells significantly enhanced the abilities of proliferation, migration, angiogenesis, and vascular endothelial-derived growth factor (VEGF) secretion in HUVECs. miR-1247-3p was highly expressed in exosomes derived from T24 and UM-UC-3 cells, and exosomes derived from miR-1247-3p inhibitor-transfected cells reduced HUVEC viability, migration, tube formation, and VEGF level. FOXO1 was confirmed as a direct target of miR-1247-3p. Rescue assays suggested that the effect of miR-1247-3p inhibition on the viability, migration, and angiogenesis of HUVECs was partly abrogated by the knockdown of FOXO1. Our data suggest that miR-1247-3p is up-regulated in tumor-derived exosomes, thereby inhibiting FOXO1 expression and facilitating angiogenesis in bladder cancer.	bladder